Glucosamine organic acid adducts

ABSTRACT

The invention pertains to compositions containing glucosamine and organic acids, methods of making such compositions and methods of using such compositions.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims priority from U.S. provisional application No.60/339,004 filed Dec. 7, 2001, which is herein incorporated byreference.

FIELD

The invention provides compositions containing glucosamine organic acidadducts and methods of making and using the same.

BACKGROUND

Presently the majority of the glucosamine available for use as a dietarysupplement is in the form of the salt glucosamine hydrochloride or thesalt glucosamine sulfate. Formulators add glucosamine as an individualingredient to a multi-component formulation, such as tablets, or dietarysupplements such as supplement bars or supplement beverages. Hence, manyproduction processes that incorporate glucosamine into final productshave separate vessels (hoppers) that allow glucosamine to beindividually added.

In order to increase efficiency of production (i.e. reduce the number ofvessels) formulators sometimes use dry blends of ingredients that arethen added during the production process from a single vessel. Dryblends are mixtures of two distinct ingredients that act independentlyof each other. Unfortunately, containers of dry blends do not maintainhomogeneity and therefore, the ingredients segregate to different partsof the container due to the different physical characteristics of theindividual ingredients. Glucosamine hydrochloride and glucosaminesulfate are also known to have a bitter taste, which taste can leadconsumers to search for better tasting alternatives.

Therefore, a need exists for a bulk glucosamine composition that can betaken as a dietary supplement, used to formulate complex dietarysupplements, and/or used as a food ingredient, and which has a bettertaste profile.

SUMMARY

Glucosamine organic acid adducts (GOA) are disclosed. The disclosedadducts mainly contain, glucosamine, one or more organic acids or saltsthereof, moisture, one or more balancing ions, and one or more inorganicsalts. For example the GOA may contain glucosamine and 1, 2, 3, 4, or 5different organic acids, which together form crystals with glucosamine.Certain embodiments of the composition typically have a substantiallyuniform or homogenous concentration of glucosamine and organic acidthroughout. The uniformity can be obtained, for example, bycrystallizing or surface crystallizing the glucosamine and one or moreorganic acids. The GOAs described herein can be used in a variety ofapplications, such as food ingredients and/or dietary supplements. TheGOAs are useful for, among other things, tableting, especially formaking chewable tablets, and altering the taste profiles of glucosaminecontaining compositions.

Certain embodiments of the GOA compositions are substantiallyhomogeneous. The GOA compositions can be combined with other materials,including for example crystalline materials, and/or may be used as aningredient in food products or nutritional supplements. The GOAcompositions can be also used in tablet formulations.

The ratio of glucosamine to organic acids in the GOA embodiments canvary. For example, the glucosamine concentration can be greater than, orequal to, the total organic acid concentration. In alternativeembodiments, the total organic acid concentration is greater than theglucosamine concentration. Exemplary embodiments of GOA compositions cancontain glucosamine to total organic acid concentration (G:OA) ratiossuch as 100:1, 75:1, 50:1, 25:1, 10:1, 5:1, 1:1, 1:5, 1:10, 1:25, 1:50,1:75, or 1:100. Alternatively, ranges between these ratios, such as fromabout 100 to about 75:1, or from about 75 to about 50:1 can be used. Themoisture content of the GOA can also vary. For example, the moisturecontent can be less than about 20 weight percent of the GOA or less than15, 10, 5, 3, 2 or 1 weight percent of the GOA. However, other moistureconcentrations are also useful.

Methods for producing GOA are also disclosed. As known to persons ofordinary skill in the art, once the GOAs are disclosed, various methodscan be used to produce such GOA. Certain example methods involve addingone or more organic acids to a solution containing glucosamine, removingwater from the solution until crystals form and collecting the crystals,wherein the crystals contain the glucosamine organic acid adduct. Othermethods provided by the invention involve adding a base, such as NaOH,KOH, or the salt form of an organic acid to the solution containingglucosamine and/or organic acids.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a spectrum from a FTIR (Fourier Transform Infrared)Spectrometry analysis of an embodiment of the glucosamine-citrate adductas made by the process disclosed in Example 1.

FIG. 2 is an FTIR spectrum of a prior art glucosamine hydrochloride (Lot27126A), CAS No. 66-84-2 (Phanstiehl Laboratories, Inc., Waukegan, Ill.)used as a control.

FIG. 3 is an FTIR spectrum of citric acid produced at Cargill, Inc.,Eddyville, Iowa, CAS No. 77-92-9 used as a control.

I. DETAILED DESCRIPTION

A. Process for Obtaining Glucosamine

Glucosamine for use in the embodiments of the GOAs may be from anysuitable source, such as bacterial biomass, or chitin containing sourcessuch as fungal biomass or shellfish. Free glucosamine can be produced bya variety of methods and from various sources as is well known to thoseof ordinary skill in the art. For example, free glucosamine can beproduced by treating glucosamine hydrochloride (or sulfate) in asolution either with an inorganic base, for example, LiOH, NaOH, KOH,CaO, and/or Ca(OH)₂, or an organic base such as sodium citrate. Theamount of base used depends on the glucosamine source and the chosenbase(s). For example, from about 0 to about 1.1 equivalents of base toglucosamine may be used. Alternatively, the amount of base used may bedetermined from the quantity of organic acid that is to be used to makethe GOA, for example see the embodiment disclosed in Example 2. The pHof the solution may be kept below about 11, to avoid oxidation and/orcolor formation. Other pH levels may also be employed.

A base can be added to the solution containing glucosamine in variousmanners as is known to those of ordinary skill in the art. For example,the base may be added as a solid, slurry, and/or solution. Adding thebase as a solution or as a slurry may avoid extreme localized heatfluctuations and/or localized reactions. Maintaining the temperature ofthe solution containing glucosamine at about 37° C. or less may helpstabilize free glucosamine.

Glucosamine can be isolated from the solution containing glucosaminedescribed above using various methods known to those skilled in the art,such as precipitation, extraction, or chromatographic methods. However,in the experiments detailed below free glucosamine in solution was used.The free glucosamine in basic solution may be unstable, and the compoundmay oxidize or decompose easily in solution developing color at arelatively high pH.

B. Making Glucosamine-Organic Acid Adduct (GOA)

The glucosamine organic acid adduct (GOA) can be obtained for example,by adding an organic acid to a glucosamine hydrochloride solution, aglucosamine sulfate solution, or a free glucosamine solution. Organicacids such as acetic acid, ascorbic acid, formic acid, lactic acid,maleic acid, malic acid, propionic acid, succinic acid, fumaric acid,citric acid, nicotinic acid, or combinations thereof may be used.Addition of acid can be done at ambient temperature (25° C.-37° C.), orat lower temperatures.

Forming certain embodiments of GOA may be accomplished using mono-, di-,and/or polyprotic acids. The amount of acid used may be, for example,from about 0.2 molar ratio to about 5 molar ratio to glucosamine, butmore or less acid may be desirable for specific applications. Additionof organic acid can be done either in solution or with the help of anionic exchange chromatographic system, for example an ion exchange resinloaded with the conjugate base of the organic acid. If it is desired,de-salting may be done, for example, through membrane filtration,dialysis, or re-crystallization.

After enough acids are added to the mixture, the glucosamine is stableenough to be treated at elevated temperatures. The mixture can then bestirred for between about 0.5 to about 24 hours, and/or kept at elevatedtemperature to facilitate the formation of the GOA.

The resulting mixture containing glucosamine and organic acid can thenbe evaporated by any suitable means to concentrate the solution andallow crystals to form. Evaporation is generally done under vacuumbetween about 5 and about 26 inches of mercury and at elevatedtemperature (between about 35° C. to about 60° C.) to evaporate thewater. The ratio of organic acid to glucosamine can be varied dependingon the evaporation process. Virtually all of the water is removed toproduce wet crystals, the ratio of acid to glucosamine will be the sameas the starting mixture.

In another embodiment, the evaporation can be stopped after crystalsform but before the water is completely removed. In this case, the ratioof glucosamine to acid will depend on the relative solubilities of theglucosamine and the organic acid. The final product composition can becontrolled by balancing the starting concentration of the organic acidand glucosamine, the solubilities of the organic acid and theglucosamine, and the extent of evaporation.

In yet another embodiment, a water-miscible solvent, such as methanol,ethanol, or isopropanol, is used. The organic solvent decreases thesolubilities of the organic acid and glucosamine, and provides forcontrol of the product composition.

The mixture containing organic acid and glucosamine can stand for aperiod of time at the desired temperature to control the crystallizationprocess. This is a process commonly referred to as digestion, whichresults in larger crystals. The crystallization process is anequilibrium process, and smaller crystals, having larger surface areas,tend to dissolve more rapidly than larger crystals. The dissolvedcomponents tend to crystallize onto the larger crystals.

Crystals obtained through crystallization can be separated using anysuitable separation method, for example, decantation, filtration orcentrifugation.

C. Characterization of the Glucosamine-Organic Acid Adduct (GOA)

1. Description of GOA

A glucosamine organic acid (GOA) adduct as described herein is a dry,crystalline adduct that contains primarily glucosamine and one or moreorganic acids, such as citric acid, propionic acid, acetic acid,ascorbic acid, lactic acid, amino acid such as glutamic acid, or otherorganic acids. As used herein adduct refers to a complex in which theglucosamine is bound with an organic acid without significantly changingthe chemical character of either the glucosamine or the organic acid.For example components of the adducts are non-covalently bonded througheither dispersive or non-dispersive bonding, such as ionic bonds, Vander Waal interactions, and/or hydrogen bonding. Therefore, a GOA isdistinct from dry blends that contain pure glucosamine crystals and pureorganic acid crystals.

Dry blends are mixtures that contain dry glucosamine hydrochloride ordry glucosamine sulfate and dry organic acid. Generally, dry blends areprepared by adding dry forms of glucosamine and organic acid togetherand mixing. Therefore, dry blends contain mixtures of glucosaminecrystals and organic acid crystals that can be separated, however, thisis not the case for GOA.

The GOA crystals are distinct from pure glucosamine hydrochloridecrystals (which are rhomboid or bipyramidal in shape), and pure organicacid crystals such as citrate crystals (which are rounded needle shapewith a translucent appearance). Some embodiments of GOA crystals withhigh glucosamine content show only some pyramidal characteristics.Similarly, some embodiments of GOA crystals containing highconcentrations of citrate are slightly translucent, but clearlydistinguishable from pure citrate crystals.

As mentioned above, in addition to glucosamine and organic acid, someembodiments of the GOA can contain balancing ions that provide chargeneutrality in the adduct. These ions can be cations, such as lithium,sodium or potassium, and/or anions such as chloride, bromide, sulfate,or organic anions, such as the conjugate base of the organic acid usedto prepare the adduct.

Another method of differentiating between GOA and dry blendedglucosamine organic acid mixtures is by testing for homogeneity.Homogeneity as used herein describes that a container of GOA containsthe same proportion of the components of the GOA throughout thecontainer regardless of particle size. In other words, a sample takenfrom the top of a container of GOA is substantially similar to a sampletaken from the bottom of the same container. Dry blends of glucosaminehydrochloride and citrate fail to form stable homogeneous mixturesbecause the two components segregate due to differences in crystal size,density and shape.

Another method of determining that a GOA sample contains a homogeneouscrystalline material is by using standard light microscopy. One ofordinary skill in the art will appreciate that test samples can be takenfrom different sections of a large sample or container of GOA. Thesetest samples can be viewed under a light microscope. The crystals in thetest samples will look substantially the same and, therefore, the largesample is deemed homogeneous. This is in contrast to what would be seenif a dry blend was viewed. Test samples taken from different portions ofa dry blend would show that the proportion of glucosamine crystals tothe organic acid crystals is different between test samples.

Homogeneity of a GOA preparation can be expressed statistically withrespect to the standard deviations of the method(s) used to analyze thesamples. A preparation of an embodiment of a GOA is consideredhomogeneous if the differences between multiple samples from a singlecontainer vary by no more than about 130% to about 110% of theanalytical confidence limit. Homogeneity can be described as“substantial” when the samples from a single container vary by no morethan 130% of the analytical confidence limit. Homogeneity can bedescribed as “significant” when the samples from a single container varyby no more than 120% of the analytical confidence limit. Homogeneity canbe described as “high” when the samples from a single container vary byno more than 110% of the analytical confidence limit. The confidencelimit for an analytical method is a well-known statistical figure ofmerit (Chemical Separations and Measurements, D. G. Peters, J. M. Hayes,and G. M. Hieftie, 1974 W. B. Saunders company, Philadelphia, Pa. ISBN0-7216-7203-5, chapter 2). Values differing by quantities less than orequal to the confidence limit are considered statistically equivalent.The confidence limit for a method is calculated from the method varianceusing a Student t-table, and the general formula CL=±t_(α,φS), where αis the uncertainty, φ is the number of degrees of freedom (number ofmeasurements −2) and S is the standard deviation of the series ofmeasurements.

Homogeneity of GOAs compared to dry-blended mixtures can be determinedby proximate analysis to determine the glucosamine and organic acidcontent of multiple samples selected randomly throughout a container. Acomparison of a dry blend of glucosamine hydrochloride and citric acid,and a GOA comprising the same species is provided in Example 7. The GOAwas prepared eleven months prior to homogeneity testing. The dry blendwas freshly prepared. The citric acid content of the dry blend variedfour times as much as the citric acid content of the GOA. The variationin citric acid measurements in GOA was no greater than that for purecitric acid.

2. Uses of GOA

Embodiments of the GOA are useful for making tablets, especiallychewable tablets. Homogeneity is a desirable trait for dry componentsthat are used for making tablets, powdered nutritional supplements,and/or food additives. U.S. Pat. No. 3,619,292 (herein incorporated byreference) describes several methods of making tablets. These basicmethods and other methods known in the art can be used to make tabletsthat contain embodiments of the GOA.

GOA is also desirable because it is believed that the combination oforganic acid and glucosamine will allow the glucosamine to haveincreased bioavailability, similar to the increased calciumbioavailability shown for calcium citrate compounds described in U.S.Pat. No. 4,814,177. Bioavailability can be defined as the relativeamount of the dose of a drug or other substance reaching the systemiccirculation. One method of testing for bioavailability is to administera known quantity of a substance to a subject and then test for theamount of that substance which is excreted from the subject's body.Methods of testing for the bioavailiability of glucosamine are wellknown in the art. For example, Setnikar and Rovati,Arzneimittelforschung 51: 699-725, 2001, describe a method that can beutilized to compare the bioavailability of GOA to glucosaminehydrochloride or glucosamine sulfate.

There are several reasons why homogeneous compositions are advantageouswhen they are used to formulate pharmaceuticals as described in U.S.Pat. Nos. 6,075,608, 5,054,332, and 5,946,088. For example, homogeneouscompositions allow for consistent dosages of active ingredients (such asglucosamine) to be delivered to subjects. Moreover, homogeneouscompositions allow for consistent absorption by the body.

II. EXAMPLES

The following examples serve as illustrations only, and should not serveto limit the scope of protection afforded in the claims. These examplesprovide methods of making and testing glucosamine organic acid adducts.

Example 1 Production of Glucosamine Citrate with Control of Amine-AcidRatio in Product

The procedure below can be used to prepare glucosamine citrate havingvarious ratios of glucosamine:citrate. The ratios are controlled by themolar ratios in the starting solution, and may range from 10:1 to 1:5glucosamine:citric acid (G:C). The GOA compositions described below wereprepared using starting G:C ratios of 5:1, 3:1, 1:1, 1:2, and 1:5. Theexamples used partial crystallization rather than complete waterremoval, demonstrating the ability to use the relative solubilities ofglucosamine and the organic acid in controlling the product composition.

More specifically, 1 mole glucosamine hydrochloride (purchased fromPfansteihl Laboratories, Inc, Waukegan, Ill.) was added to 1 L deionizedwater at room temperature and stirred until there were no visible solidsleft. 2 moles of citric acid (Cargill, Inc., Eddyville, Iowa) were thenadded to the dissolved glucosamine solution, hence, creating a 1:2 G:Cratio.

The solution was then placed in a rotary evaporator under a vaccum (25inches of mercury) at 60° C. until 50-70% of the water evaporated.Crystals resulted from the evaporation step, and these crystals wereisolated by vacuum filtration at room temperature. The crystals werethen dried in open pans at room temperature.

Using the above procedure, crystals were created that contained the Wt %reflected in Table 1, below. TABLE 1 Mole ratio G:C Wt % Wt % ChlorideIn starting solution Glucosamine Wt % Citric Acid (balancing anion) 5:180.9 2.1 16.1 3:1 73.3 9.2 14.9 1:1 72.3 10.6 13.4 1:2 57.4 22.9 12.61:5 31.8 58.1 5.9

Example 2 Glucosamine Citrate from Glucosamine, Citric Acid, and NaOH

The procedure below can be used to prepare a glucosamine citrate adducthaving various ratios of glucosamine:citrate:NaOH. The ratios arecontrolled by the molar ratios in the starting solution, and may rangefrom 10:1:0 to 1:5:15 glucosamine:citric acid:NaOH. GOAs were preparedusing starting ratios of 10:2:1, 6:2:1, 2:2:1, 1:2:1, and 2:6:3. Alltested preparations used 0.5 equivalents of NaOH based on citric acid inthe starting solution. At high NaOH ratios (1 citrate:3 NaOH), thesolution becomes very dark upon heating, indicating chemical reaction ofthe amine. Other bases, such as KOH, may also be used. The GOA samplesprepared in this example used partial evaporation of water as in Example1 to illustrate the effects of relative solubilities.

A solution containing glucosamine hydrochloride and citric acid (1:2G:C) was made as described above. To that solution 1 mole of NaOH wasslowly added and mixed thoroughly at room temperature.

Crystals were formed, filtered, and dried using the techniques describedabove.

Using the above procedure crystals were created that contained the Wt %reflected in Table 2, below. TABLE 2 Mole ratio G:C Wt % Glucosamine Wt% Citric Acid Wt % Chloride 5:1 80.4 1.9 16.2 3:1 79.3 3.6 16.1 1:1 78.24.2 13.9 1:2 69.2 12.3 10.5 1:3 56.3 13.5 10.2

Example 3 GOA Preparation from Glucosamine Sulfate and Citric Acid

The procedure from Example 1 was used to prepare glucosamine citratefrom glucosamine sulfate [(GlcN)₂SO₄.2KCl] (distributed by AnhuiWorldbest, Hefei, P.R. China), and citric acid (Cargill, Inc.,Eddyville, Iowa). 0.2 mole of glucosamine sulfate was dissolved indeionized water. The citric acid (0.2 mole) was added and dissolved. Thesolution was evaporated on a rotary evaporator at 60° C. and 25 inchesof vacuum until crystals formed. The crystals were isolated by vacuumfiltration, and then air-dried at room temperature.

The composition of the GOA thus formed was 65.4 wt % glucosamine, 12.4wt % chloride, 2.5 wt % K, 3.7 wt % sulfate, and 15.2 wt % citric acid.

Example 4 GOA Preparation from Glucosamine Hydrochloride, TrisodiumCitrate, and Citric Acid

The procedure in Example 1 was adapted to prepare GOA from glucosaminehydrochloride, trisodium citrate (TSC), and citric acid, anhydrous(CAA). In this example, the trisodium citrate was used in place of thesodium hydroxide from Example 2 to neutralize the glucosaminehydrochloride.

Two 0.2 mole aliquots of glucosamine hydrochloride (PfanstielLaboratories, Inc., Waukegan, Ill.) were dissolved in deionized water,then cooled to approximately 5° C. in an ice-water bath. 0.07 mole (0.2equivalent) of trisodium citrate (Cargill, Inc., Eddyville, Iowa) wasadded to one aliquot, and then mixed until all solids dissolved. Another0.13 mole of citric acid (Cargill, Inc., Eddyville, Iowa) was added tothe solution, and then mixed until all solids dissolved.

A dry mixture of trisodium citrate and citric acid (0.07 and 0.13 moles,respectively) was added to the second aliquot of glucosaminehydrochloride solution. The solution was mixed until all solidsdissolved.

The solutions were transferred to separate rotary evaporator flasks andevaporated at 60° C. and at 25 inches of vacuum until crystals formed.The crystals were separated from the liquors by vacuum filtration, thenair-dried at room temperature. The crystals formed exhibited the Wt %composition in Table 3, below. TABLE 3 Citrate Wt % Wt % Wt % AdditionGlucosamine Citric Acid Wt % Sodium Chloride TSC, followed 70.3 11.7 1.513.8 by CA TSC and CA 72.9 9.4 1.1 14.2

Example 5 GOA Production from Glucosamine Hydrochloride and Lactic orMalic Acids

The procedure of Example 1 was used to prepare GOA using lactic or malicacids. Lactic acid (USP grade, Mallinckrodt, Paris, Ky.) was tested atmole ratios of one and two with respect to glucosamine hydrochloride.Malic acid (Parchem Trading, LID, White Plains, N.Y.) was tested at moleratios of 1, 2 and 3.

Using the procedure in Example 1, crystals were created that containedthe Wt % reflected in Table 4, below. In the first column, the lettersG, L, and M refer to glucosamine, lactic acid, and malic acid,respectively. TABLE 4 Characteristics of GOA from Lactic and Malic AcidsMole Ratio Wt % Acid Wt % Glucosamine Wt % Chloride 1G:1L 1.2 81.8 15.71G:2L 3.0 79.3 15.8 1G:1M 6.6 78.0 15.3 1G:2M 12.2 72.9 14.4 1G:3M 8.575.4 15.2The high water solubilities of malic and lactic acids compared to citricacid account for the lower acid contents of the GOAs produced in thisexample.

Example 6 Characterization and Identification of GOA

The GOA products made in Examples 1 through 5 can be analyzed forconcentration of their components by FTIR (Fourier Transform Infrared)Spectrometry. Using standard FTIR techniques well known in the art,spectra were generated (see USP-NF monograph for glucosamine, published2002). The spectra shows bands characteristic of both citric acid andglucosamine, as indicated in FIGS. 1, 2, and 3. Proximate analysis todetermine the molar ratios in the adduct is accomplished by the methodsdescribed below.

Citric acid is determined quantitatively by dissolving a known quantityof glucosamine citrate in deionized water. The solution is filteredthrough a 0.22μ filter into a HPLC vial. The sample is analyzed by HPLCusing a BioRad HPX-87H column (BioRad, City, State) and 0.01 N H₂SO₄ asthe mobile phase.

Glucosamine was determined by a total nitrogen measurement using a LECOor Antek nitrogen analyzer according to the manufacturer's instructions.Since the purity of glucosamine is known before preparing theglucosamine-citrate, a total nitrogen value can be applied.

Other inorganic species, including sodium, potassium and sulfate weredetermined by ICP-AES (inductively coupled plasma-atomic emissionspectrometry). Certified standards were used to calibrate theinstrument.

Residual chloride is determined using a potentiometric titration. Silvernitrate is the titrant, and a silver indicating electrode monitors thecourse of the titration.

Moisture was determined using either an oven at 105° C., where thepercent change in sample weight after drying is due to moisture or ahalogen moisture balance (Mettler or equivalent), which heats the samplewhile monitoring weight, stopping when weight change ceases.

Example 7 Homogeneity of GOA

A sample containing a blend comprising 20% by weight anhydrous citricacid and 80% glucosamine hydrochloride was blended by tumbling for fiveminutes. The blended sample was poured into a tray. Eight aliquots werecollected from different areas of the tray. The aliquots were diluted in0.01N H₂SO₄, and then analyzed for citric acid by the method describedin Example 6. The peak areas were normalized by the aliquot weights, andthen averaged. The relative standard deviation for the eight aliquotswas 7.7%.

The two components in the blend had similar, but not identical particlesize distributions. The natural crystal shapes of these componentsdiffer, in that citric acid crystals are needle shaped while glucosaminehydrochloride crystals are bipyramidal.

A sample of GOA from Example 2, which had been stored at roomtemperature in a flask for approximately eleven months, having 12.3%citric acid was analyzed similarly. Eight aliquots were taken from thesample. Citric acid was determined by HPLC as described above. The peakareas were normalized by the aliquot weights, and then averaged. Therelative standard deviation for the eight aliquots was 1.9%.

The analytical precision measured from eight aliquots of pure citricacid was 1.8% relative. The difference in precision between the GOA andcitric acid was negligible, demonstrating a high degree of homogeneity.In contrast, the differences in precision between pure citric acid andthe dry blend was significant, indicating a low degree of homogeneity.

Example 8 Taste of GOA

The GOA composition offers the ability to alter taste profile whencompared to glucosamine hydrochloride or glucosamine sulfate. Taste wasmeasured by conducting a “difference from control test” using a panel of7 individuals. Panelists evaluated samples by comparing glucosaminehydrochloride {(control) (Lot 27126A), CAS No. 66-84-2 (PhanstiehlLaboratories, Inc., Waukegan, Ill.)} to unmarked glucosamine organicacid samples (glucosamine citrate) in various ratios and a blind controlat 0.44% weight/weight glucosamine hydrochloride in water and reportinghow samples were the same or different. The sensory panelists found veryapparent differences in the samples as summarized below in Table 5.Samples were also rated on a 5 point scale for difference from control,0=no difference, 1=trace, 2=slight, 3=moderate, 4=strong, 5=very strong.TABLE 5 GOA Sensory Results Numerical Results Sample (Average) TasteResults Blind Control 1 Trace sweet, bitter 1G:1C 4 Strong sour, slightastringent 1G:2C 5 Very strong sour, strong astringent 1G:3C 5 Verystrong ++sour, very strong astringent

All samples were different from the control, effectively reducing thebitterness of glucosamine. “Astringent” is defined as dryness in themouth. These results indicate that an adduct of glucosamine with anorganic acid has desirable taste characteristics when compared to pureglucosamine. Organic acids that are useful for forming the adductinclude citric acid, lactic acid, malic acid, and sorbic acid (potassiumsorbate).

Example 9 Tableting of GOA

GOA has tableting characteristics similar to glucosamine, so existingglucosamine tableting equipment is sufficient for tableting GOA. Inorder to show this, tablet processing was done manually using a ChemplexManually Operated Hydraulic Press with a Chemplex Evacuable XRF SamplePellet Die Assembly. A direct compression method was utilized by adding1.794 g of glucosamine (Lot 27126A), CAS No. 66-84-2 (PhanstiehlLaboratories, Inc., Waukegan, Ill.) and 1.2 g of binder (Avicel® PH-302Microcrystalline Cellulose from FMC®) to a 50 mL tube and shakingvigorously for 10 minutes in an automated shaker, then adding 0.006 g oflubricant (magnesium stearate from Mallinckrodt) and again shaking for 3minutes, and tableting at 5 tons pressure and under <2 cm Hg of vacuum.Tablets were also prepared with this method, but GOA was used instead ofglucosamine. All tablets were comparable in regard to release from thedie, and there was no noticeable chipping or stress cracking.

Therefore, based on the enhanced flavor of GOA compared to glucosamine,the formation of chewable tablets for those who are unable to swallowlarge pills or prefer a different delivery system can be achieved.

Example 10 Preparation of GOA by Surface Crystallization

Examples 1 through 5 demonstrated GOA preparation where glucosamine andorganic acids are in solution, then crystallized as adducts. GOA can beprepared by spraying a solution of one component onto the othercomponent in solid form. The moisture is removed, resulting in GOA wherethe surfaces of the crystals contain glucosamine and organic acids, butthe solid component is never fully dissolved, such that the cores of theparticles may contain only a single component.

To prepare GOA in this manner, a rotary tumbler is partially filled withsolid glucosamine hydrochloride. The material is tumbled while a fineaerosol consisting of a 20 wt % solution of citric acid in water issprayed onto the tumbling solids. Heat is added to control evaporationrate, maintaining a moisture level too low to dissolve the glucosaminecrystals. Once the desired amount of citric acid is added, the remainingmoisture is removed before tumbling is stopped.

The GOA product produced will be homogeneous when tested at typicaldosage levels (0.1 gram or more per sample).

1. A glucosamine organic acid adduct comprising glucosamine, and one ormore organic acids.
 2. The adduct of claim 1, wherein the adduct issubstantially homogenous.
 3. The adduct of claim 1, further comprisingsalts of organic acids, moisture, one or more balancing ions, and one ormore inorganic salts
 4. The adduct of claim 1 in a tablet form.
 5. Theadduct of claim 1, wherein the molar concentration of glucosamine isgreater than or equal to the molar concentration of organic acid.
 6. Theadduct of claim 1, wherein the molar concentration of glucosamine isless than the molar concentration of organic acid.
 7. The adduct ofclaim 1 wherein the content of the moisture is less than about 20 weightpercent.
 8. The use of the adduct of claim 1 as a dietary supplement. 9.The adduct of claim 8 wherein the glucosamine and the one or moreorganic acids in the single compound are in a molar ratio of 5:1. 10.The adduct of claim 8 wherein the moisture content of said compositionis less than about 20 weight percent.
 11. The use of the adduct of claim1 as a food ingredient.
 12. The composition of claim 11 whereinglucosamine and the one or more organic acids in the single compound arein a molar ratio of 5:1.
 13. A process for producing a glucosamineorganic acid adduct comprising: forming a solution comprising an aqueousmedium, glucosamine and an organic acid; removing the aqueous medium;and collecting the crystals, wherein the crystals comprise theglucosamine organic acid adduct.
 14. The process according to claim 13,wherein substantially all of the aqueous medium is removed.
 15. Theprocess according to claim 13, further comprising adding a base to thesolution prior to removing water from the solution.
 16. The processaccording to claim 13, wherein some or all of the water is replaced by awater miscible solvent.
 17. A product created by the process of claim13.
 18. A composition consisting of glucosamine, one or more organicacids or salts thereof, moisture, one or more balancing ions, and one ormore inorganic salts.
 19. A method of forming a glucosamine organic acidadduct comprising: tumbling a dry component comprising glucosamineand/or one or more organic acids; and spraying the dry component with asolution comprising glucosamine, and/or one or more organic acids,wherein a glucosamine organic acid adduct is formed.